The overarching goal of the research described in this R21 grant application is to provide a first critical test of the novel scientific idea that a combined diet and exercise intervention may ameliorate leukocyte telomere length (LTL) in cancer survivors with nonmuscle-invasive bladder cancer (NMIBC). In this understudied population of cancer survivors, who are at high risk of recurrence and progression to life-threatening muscle- invasive bladder cancer, shorter LTL is a significant predictor of decreased survival independent of traditional prognostic variables including age, tumor grade and stage. The research is consistent with PA-15-310 ?Physical Activity and Weight Control Interventions Among Cancer Survivors: Effects on Biomarkers (R21).? The research described here will be the first to test the hypothesis that significant amelioration of LTL can be achieved by adding 250 min/wk physical activity to dietary reductions as part of a theory-based behavioral intervention in NMIBC survivors. This randomized clinical trial (RCT) will also be the first to concurrently explore biomarkers in two systemic biological pathways that contribute to telomere shortening: oxidative DNA damage and inflammatory biomarkers. The research has strong conceptual/empirical grounding and will build directly upon prior extensive diet and physical activity intervention trials by Dr. Jakicic (co-PI). Aim 1: To conduct a RCT with survivors of NMIBC to test the effects of a behavioral intervention program targeting physical activity and diet on: 1) LTL (primary [1o] outcome,) [H1.1]; and, 2) systemic biomarkers of oxidative stress and inflammatory processes (secondary [2o] outcomes) [H1.2], using a randomized design with two groups: 1) Diet only [DIET], final n=40; 2) Diet plus physical activity [DIET-PA], final n=40), stratified by classic prognostic risk phenotypes and assessed three times (baseline, 3mo, 6mo). Aim 2: To concurrently investigate three health behavior-related pathways hypothesized to underlie intervention effects on LTL in NMIBC survivors: 1) obesity; 2) physical activity; and 3) cardiorespiratory fitness to explore relationships between those variables and the 1o [H2.1] and 2o outcomes [H2.2]. This aim is not dependent on Aim 1 results; here relationships are examined independent of the intervention. Aim 3: To explore hypothesized relationships between the 1o and 2o outcomes independently [H3.1], and as part of mediational analyses of results found in Aim 1 [H3.2] and Aim 2 [H3.3]. Impact: With a focus on an understudied cancer survivor population at high risk for recurrence and progression, the planned research will have a ?sustained powerful influence on the research fields involved? (PA-15-310). Anticipated results will support a subsequent fully powered multisite trial to confirm generalizability, and open new areas of research into the underlying molecular mechanisms and into the clinical consequences of behavioral interventions targeting BMI and physical activity to ameliorate LTL in survivors of NMIBC and potentially, other cancers as well.